title: The voltage-gated sodium channel nav1.8 is expressed in human sperm.
abstract: The role of Na(+) fluxes through voltage-gated sodium channels in the regulation of sperm cell function remains poorly understood. Previously, we reported that several genes encoding voltage-gated Na(+) channels were expressed in human testis and mature spermatozoa. In this study, we analyzed the presence and function of the TTX-resistant VGSC α subunit Nav1.8 in human capacitated sperm cells. Using an RT-PCR assay, we found that the mRNA of the gene SCN10A, that encode Na v1.8, was abundantly and specifically expressed in human testis and ejaculated spermatozoa. The Na v1.8 protein was detected in capacitated sperm cells using three different specific antibodies against this channel. Positive immunoreactivity was mainly located in the neck and the principal piece of the flagellum. The presence of Na v1.8 in sperm cells was confirmed by Western blot. Functional studies demonstrated that the increases in progressive motility produced by veratridine, a voltage-gated sodium channel activator, were reduced in sperm cells preincubated with TTX (10 μM), the Na v1.8 antagonist A-803467, or a specific Na v1.8 antibody. Veratridine elicited similar percentage increases in progressive motility in sperm cells maintained in Ca(2+)-containing or Ca(2+)-free solution and did not induce hyperactivation or the acrosome reaction. Veratridine caused a rise in sperm intracellular Na(+), [Na(+)]i, and the sustained phase of the response was inhibited in the presence of A-803467. These results verify that the Na(+) channel Na v1.8 is present in human sperm cells and demonstrate that this channel participates in the regulation of sperm function.
authors.affiliation: Instituto de Investigaciones Químicas (IIQ), CSIC - Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cejudo-Roman
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Pinto
authors.forename: Nerea
authors.initials: N
authors.lastname: Subirán
authors.forename: Cristina G
authors.initials: CG
authors.lastname: Ravina
authors.forename: Manuel
authors.initials: M
authors.lastname: Fernández-Sánchez
authors.forename: Natalia
authors.initials: N
authors.lastname: Pérez-Hernández
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pérez
authors.forename: Alberto
authors.initials: A
authors.lastname: Pacheco
authors.forename: Jon
authors.initials: J
authors.lastname: Irazusta
authors.forename: Luz
authors.initials: L
authors.lastname: Candenas
mesh_terms: D000704:Analysis of Variance; D000814:Aniline Compounds; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005663:Furans; D006801:Humans; D008297:Male; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism; D013075:Sperm Capacitation / Q000502:physiology; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000378:metabolism*; D014701:Veratridine / Q000494:pharmacology
chemical_list: C520740:A 803467; D000814:Aniline Compounds; D017931:DNA Primers; D005663:Furans; D062559:NAV1.8 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C568317:SCN10A protein, human; D014701:Veratridine; D012964:Sodium